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EP2575961B1 - Système de stimulation spatialement sélective du nerf vague - Google Patents

Système de stimulation spatialement sélective du nerf vague Download PDF

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Publication number
EP2575961B1
EP2575961B1 EP11725562.0A EP11725562A EP2575961B1 EP 2575961 B1 EP2575961 B1 EP 2575961B1 EP 11725562 A EP11725562 A EP 11725562A EP 2575961 B1 EP2575961 B1 EP 2575961B1
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EP
European Patent Office
Prior art keywords
stimulation
vagus nerve
electrode
electrical stimulation
branch
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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EP11725562.0A
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German (de)
English (en)
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EP2575961A1 (fr
Inventor
Paul B. Yoo
Warren M. Grill
Juan Gabriel Hincapie Ordonez
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Cardiac Pacemakers Inc
Duke University
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Cardiac Pacemakers Inc
Duke University
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Publication of EP2575961A1 publication Critical patent/EP2575961A1/fr
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/36053—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for vagal stimulation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
    • A61N1/36114—Cardiac control, e.g. by vagal stimulation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/36128—Control systems
    • A61N1/36146—Control systems specified by the stimulation parameters
    • A61N1/36167—Timing, e.g. stimulation onset
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A61B5/316—Modalities, i.e. specific diagnostic methods
    • A61B5/389—Electromyography [EMG]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/40—Detecting, measuring or recording for evaluating the nervous system
    • A61B5/4029—Detecting, measuring or recording for evaluating the nervous system for evaluating the peripheral nervous systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/0551—Spinal or peripheral nerve electrodes
    • A61N1/0556—Cuff electrodes

Definitions

  • This document relates generally to neurostimulation and more particularly to spatially selective vagus nerve stimulation for substantially activating one or more target nerve branches without substantially activating one or more non-target nerve branches.
  • Vagus nerve stimulation has been applied to modulate various physiologic functions and treat various diseases.
  • One example is the modulation of cardiac functions in a patient suffering heart failure or myocardial infarction.
  • the myocardium is innervated with sympathetic and parasympathetic nerves including the cardiac branches of the vagus nerve.
  • Activities in the vagus nerve including artificially applied electrical stimuli, modulate the heart rate and contractility (strength of the myocardial contractions).
  • Electrical stimulation applied to the vagus nerve is known to decrease the heart rate and the contractility, lengthening the systolic phase of a cardiac cycle, and shortening the diastolic phase of the cardiac cycle. This ability of VNS is utilized, for example, to control myocardial remodeling.
  • VNS is also known to be effective in treating disorders including, but not limited to, depression, anorexia nervosa/eating disorders, pancreatic function, epilepsy, hypertension, inflammatory disease, and diabetes. Because many physiological functions are controlled or affected by the neural activities in the vagus nerve, there is a need to control VNS for the desirable functional outcome while minimizing side effects.
  • WO 2010/031406 A1 discloses a medical device for analyzing cardiac related input signals.
  • the device is capable of receiving an ECG-signal and a nerve activity signal, such as vagus nerve signal in order to detect a cardiac related neural activity, such as epilepsy.
  • the device is programmed for detecting a trigger feature (e.g. the R-peak) in the signal and extracting a nerve activity signal segment from the nerve activity signal in response to detecting the trigger feature.
  • An activity related feature is generated either based on a combined signal obtained from a number of nerve activity signal segments, or as a segment-based activity related feature obtained from a number of nerve activity signal segments.
  • the device is adapted for comparing the activity related feature to a predefine criterion in order to detect the cardiac related neural activity.
  • delivery of electrical stimulation pulses is controlled to substantially activate one or more target branches of the vagus nerve without substantially activating one or more non-target branches.
  • electrical stimulation pulses are delivered to an electrode placed on or adjacent to a first branch of the vagus nerve.
  • the first branch is separate from a second branch of the vagus nerve and selected to allow for substantial activation of one or more target branches of the vagus nerve by the electrical stimulation pulses without substantially activating the second branch.
  • electrical stimulation pulses are delivered to an electrode placed on a portion of a cervical vagus nerve trunk or a portion of a thoracic vagus nerve (tVN).
  • the delivery of the electrical stimulation pulses is controlled such that one or more target branches of the vagus nerve are activated by the electrical stimulation pulses without causing contraction of a laryngeal muscle innervated by a recurrent laryngeal nerve (RLN).
  • RNN recurrent laryngeal nerve
  • a system for stimulating the vagus nerve includes an electrode, a neural sensing circuit, a myoelectric sensing circuit, and a neurostimulator.
  • the electrode is placed on a first branch of the vagus nerve to allow for delivery of electrical stimulation pulses to the first branch.
  • the neural sensing circuit senses a stimulation-evoked electroneurographic (ENG) signal representative of a response of the vagus nerve to the electrical stimulation pulses.
  • the myoelectric sensing circuit senses a stimulation-evoked electromyographic (EMG) signal representative of a response of a muscle to the electrical stimulation pulses, the muscle innervated by a second branch of the vagus nerve.
  • the neurostimulator includes a stimulation circuit and a stimulation control circuit.
  • the stimulation circuit delivers the electrical stimulation pulses to the first branch through the electrode.
  • the stimulation control circuit controls the delivery of the electrical stimulation pulses using a plurality of stimulation parameters and includes a parameter adjuster that allows for adjustment of one or more stimulation parameters of the plurality of stimulation parameters using the ENG signal and the EMG signal.
  • FIG. 7 is a flow chart illustrating an embodiment of another method of spatially selective VNS.
  • references to “an”, “one”, or “various” embodiments in this disclosure are not necessarily to the same embodiment, and such references contemplate more than one embodiment.
  • VNS Vagus nerve stimulation
  • the vagus nerve originates in the medulla and targets multiple organs in a person's body through a complex functional innervation pattern.
  • visceral organs such as the esophagus, gastrointestinal tract, kidney and pancreas
  • thoracic organs such as the heart and lungs
  • RLN thoracic branch of vagus
  • RLN voluntary muscles of the neck and multiple segments of the upper airway
  • VNS vagus nerve trunk
  • the cervical vagus nerve trunk contains approximately 20,000 myelinated neurons and an even greater number of unmyelinated neurons.
  • Both the human and canine vagus nerves also share a common classification scheme defined by the diameter of nerve fibers. This is based on the classical designation of A (myelinated), B (myelinated parasympathetic) and C (unmyelinated) type fibers, as summarized in Table 1.
  • Table 1 Summary of Vagus Nerve Fiber Type Properties.
  • VNS therapy a typical site of electrode implantation for VNS therapy is at the cervical spinal level between the thyroid cartilage and the sternum of the patient.
  • the vagus nerve contains a wide array of nerve fibers, as summarized in Table 1.
  • stimulation parameters used for VNS therapy are largely determined by titrating the various temporal properties of the electrical pulses (e.g., amplitude, frequency, duty cycle).
  • amplitude, frequency, duty cycle e.g., amplitude, frequency, duty cycle.
  • stimulation-evoked side effects such as voice hoarseness, coughing, and pain, remain a problem in applying VNS therapy.
  • VNS VNS
  • delivering electrical stimulation to the vagus nerve through bipolar helical nerve cuff electrode is known to result in non-selective activation of all nerve fibers within the nerve trunk, and hence little control over unintended generation of side-effects including unintended laryngeal activities.
  • spatially selective activation of vagus nerve branches refers to activation of one or more selected (or specified) vagus nerve branches by delivering electrical stimulation to a space, such as a particular segment or branch of the vagus nerve, identified to allow for activation of the one or more selected vagus nerve branches without causing an unwanted side effect such as activated of a non-selected vagus nerve branch.
  • the electrical stimulation is delivered to activate one or more target nerve pathways while minimizing activation of one or more non-target nerve pathways associated with stimulation-evoked side effects.
  • VNS is delivered to a thoracic vagus nerve (tVN) in a location separate from the RLN to allow placement of an electrode on the tVN but isolated from the RLN, such that the delivery of the electrical stimulation through this electrode results in desirable modulation of cardiovascular functions without evoking unwanted laryngeal activities.
  • tVN thoracic vagus nerve
  • Surgical separation of a portion of the tVN from the RLN may be required to create adequate space for such electrode placement.
  • the topographical organization of the nerve fascicles of the cervical vagus nerve trunk allows target selection using a single multi-contact nerve electrode.
  • the contacts in the nerve electrode are selected for delivering VNS to result in the desirable modulation of cardiovascular functions without evoking the unwanted side effects caused by activation of one or more non-targeted fibers of the vagus nerve.
  • efferent laryngeal muscle contraction is discussed as a specific example of the unwanted side effects to be avoided using the present method and system, the present subject matter applies to control of unwanted side effects by spatially selective activation of vagus nerve branches.
  • Another example of such unwanted side effects to be avoided using the present method and system includes airway reflexes evoked by (1) direct activation of afferent RLN fibers and/or (2) indirect activation of afferent RLN activity generated by efferent laryngeal muscle contractions.
  • FIG. 1 is an illustration of an embodiment of a VNS system 100 and portions of an environment in which system 100 is used.
  • FIG. 1 shows a portion of a vagus nerve 101 having segments or branches including a cervical vagus nerve trunk 102, a tVN 104, and an RLN 106.
  • the physical separation between tVN 104 and RLN 106 after they diverge from cervical vagus nerve trunk 102 allows placement of a stimulation electrode 136 on tVN 104.
  • Electrode 136 allows for delivery of VNS to tVN 104, which innervates thoracic organs, including a heart 105, and abdominal organs through further branches of the vagus nerve, without activating the RLN, which innervates laryngeal muscles (represented in FIG. 1 by a laryngeal muscle 107).
  • the physical separation between tVN 104 and RLN 106 may be created or partially created by surgery to allow for proper placement of electrode 136 without affecting neural conduction within these nerve branches.
  • tVN 104 and RLN 106 are longitudinally separated by dissecting the portion of the vagus nerve trunk including these two branches to the location where fibers of tVN 104 and RLN 106 diverge, at approximately the level of the subclavian artery.
  • electrode 136 is placed on tVN 104 within about one centimeter from the location where tVN 104 and RLN 106 diverge.
  • a portion of a nerve trunk such as a vagus nerve trunk including a first branch and a second branch is dissected to separate the first and second branches.
  • the first branch controls one or more physiological functions of a patient.
  • the second branch controls one or more other physiological functions of the patient.
  • the first branch includes the stimulation site to which the electrical stimulation is delivered.
  • the second branch is a non-target branch that is not intended to be activated by the electrical stimulation pulses.
  • the one or more target branches which include but are not limited to the first branch, are intended to be activated by the electrical stimulation.
  • the stimulation electrode is placed on the first branch to allow for delivery of electrical stimulation to activate one or more target branches of the nerve trunk (including the first branch) without activating the second branch.
  • system 100 includes an implantable medical device 110 electrically coupled to electrode 136 through an implantable lead 130.
  • Implantable medical device 110 includes a neurostimulator 120 encapsulated by an implantable housing 112, and a header 114 attached to implantable housing 112 and providing for connection to lead 130.
  • Neurostimulator 120 is discussed below with reference to FIG. 2 .
  • implantable medical device 110 is a neurostimulator.
  • implantable medical device 110 in addition to neurostimulator 120, implantable medical device 110 includes one or more of a cardiac pacemaker, a cardioverter/defibrillator, a drug delivery device, a biologic therapy device, and any other monitoring or therapeutic devices.
  • lead 130 includes a proximal end 132, a distal end 133, and an elongate body 131 coupled between proximal end 132 and distal end 133.
  • Proximal end 132 is configured to be connected to implantable medical device 110.
  • Distal end 133 includes, or is otherwise coupled to, electrode 136.
  • Electrode 136 is a bipolar nerve cuff electrode. In another embodiment, electrode 136 is a monopolar nerve cuff electrode, and another electrode such as a portion of implantable housing 112 is used. In various embodiments, electrode 136 includes any form of electrode that allows for activation of tVN 104 by electrical stimulation delivered from neurostimulator 120.
  • FIG. 1 illustrates the embodiment in which the placement of electrode 136 on tVN 104 allows for VNS to modulate cardiovascular functions without evoking unwanted laryngeal activities
  • the present subject matter generally includes selective activation of vagus nerve branches by selecting the sites to which the electrical stimulation pulses are delivered through multiple electrodes or a multi-contact electrode.
  • a multi-contact electrode may be placed in cervical vagus nerve trunk 102, cranial to the location where tVN 104 and RLN 106 diverge. Stimulation is delivered through various combination of contacts of the multi-contact electrode to select one or more contacts allowing for the VNS to substantially activate tVN 104 without substantially activating RLN 106.
  • FIG. 2 is a block diagram illustrating an embodiment of an electrode 236 and a neurostimulator 220.
  • Electrode 236 represents an embodiment of electrode 136.
  • Neurostimulator 220 represents an embodiment of neurostimulator 120.
  • Neurostimulator 220 includes a stimulation circuit 240 and a stimulation control circuit 242.
  • Stimulation circuit 240 produces electrical stimulation pulses and delivers the electrical stimulation pulses to electrode 236.
  • Stimulation control circuit 242 controls the delivery of the electrical stimulation pulses using a plurality of stimulation parameters and includes a parameter adjuster 244 and a storage circuit 246.
  • Parameter adjuster 244 allows for adjustment of one or more stimulation parameters of the plurality of stimulation parameters such that the intensity of the electrical stimulation pulses is provided for substantially activating one or more target branches of a nerve such as the vagus nerve without substantially activating one or more non-target branches of the nerve.
  • the plurality of stimulation parameters includes pulse amplitude, pulse width, pulse frequency, duty cycle, cycle unit, and stimulation duration.
  • the pulse amplitude is the amplitude of each electrical stimulation pulse specified as voltage (e.g., for constant-voltage pulse) or current (e.g., for constant-current pulse).
  • the pulse width is the duration of each electrical stimulation pulse.
  • the pulse frequency is the frequency at which the electrical stimulation pulses are delivered and may also be specified as an inter-pulse interval being the time interval between successive pulses.
  • the duty cycle is the ratio of a stimulation interval to the cycle unit.
  • the electrical stimulation pulses are delivered during only the stimulation interval.
  • the stimulation duration is the duration of a delivery of neurostimulation therapy.
  • the cycle unit and the stimulation durations may be specified by time or number of pulses, and the duty cycles may be specified by time or number of pulses in each cycle unit.
  • pulse delivered at a pulse frequency of 20 Hz at a duty cycle of 10% and a unit cycle of 1 second is equivalent to "pulses delivered at a pulse frequency of 20 Hz at a duty cycle of 2 pulses per unit cycle of 20 pulses".
  • Storage circuit 246 stores values for the plurality of stimulation parameters. In one embodiment, storage circuit 246 stores values of the one or more stimulation parameters selected to substantially activate the one or more target branches of the nerve without substantially activating the one or more non-target branches of the nerve. In one embodiment, a value of the pulse amplitude is selected to substantially activate the one or more target branches of the nerve without substantially activating the one or more non-target branches of the nerve, and stored in storage circuit 246.
  • the circuit of neurostimulator 220 is implemented using a combination of hardware and software.
  • stimulation control circuit 242 may be implemented using an application-specific circuit constructed to perform one or more particular functions or a general-purpose circuit programmed to perform such function(s).
  • a general-purpose circuit includes, but is not limited to, a microprocessor or a portion thereof, a microcontroller or portions thereof, and a programmable logic circuit or a portion thereof.
  • FIG. 3 is a flow chart illustrating an embodiment of a method 300 of spatially selective VNS. In one embodiment, method 300 is performed using system 100 including its embodiments discussed in this document.
  • a portion of the vagus nerve including a first branch and a second branch is longitudinally dissected and separated, without damaging the normal neural conduction in these branches.
  • an electrode such as a nerve cuff electrode, is placed on or adjacent to the first branch.
  • electrical stimulation pulses are delivered to the first branch through the electrode placed on the first branch.
  • the delivery of the electrical stimulation pulses is controlled to substantially activate one or more target branches of the vagus nerve, including the first branch, without substantially activating the second branch.
  • the one or more stimulation parameters are determined by monitoring neural signals and/or myoelectric signals indicative of the activation of the one or more target branches and the second branch. Surgical separation at 310 is not necessary if the electrode can be placed on or adjacent to the first branch to allow substantial activation of the one or more target branches of the vagus nerve, including the first branch, without substantially activating the second branch.
  • substantially activating a nerve means causing a detectable stimulation-evoked neural response.
  • stimulation-evoked neural response may be detected, for example, by sensing neural traffic in the nerve and/or sensing a signal indicative of a physiological function modulated by the neural traffic.
  • FIG. 4 is a flow chart illustrating an embodiment of a method 400 of spatially selective VNS.
  • Method 400 includes an embodiment of method 300 with the first branch of the vagus nerve being tVN 104 and the second branch of the vagus nerve being RLN 106.
  • method 400 is performed using system 100 including its embodiments discussed in this document.
  • electrical stimulation pulses are delivered to tVN 104, which has been longitudinally separated from RLN 106.
  • the intensity of the electrical stimulation pulses is controlled for substantially activating one or more target branches of the vagus nerve without causing contraction of a laryngeal muscle that is innervated by RLN 106.
  • this intensity is determined by sensing signals representative and/or indicative of the neural responses to the delivery of the stimulation pulses.
  • a stimulation-evoked electroneurographic (ENG) signal representative of a response of the cervical vagus nerve trunk to the electrical stimulation pulses is sensed, and a stimulation-evoked electromyographic (EMG) indicative of the response of the RLN to the electrical stimulation pulses is sensed.
  • the one or more target branches of the vagus nerve are considered to be substantially activated when the amplitude of the ENG signal exceeds a specified ENG threshold.
  • the contraction of a laryngeal muscle is not considered to be occurring, or the RLN is not considered to be activated, when the amplitude of the EMG signal does not exceed a specified EMG threshold.
  • the intensity of the electrical stimulation pulses is determined by adjusting the pulse amplitude and/or the pulse width and observing the effect of the adjustment on the amplitude of the ENG signal and the amplitude of the EMG signal.
  • FIG. 5 is an illustration of a system 500 for testing method 400.
  • the vagus nerve 101 is dissected distally to approximately the level of the subclavian artery where multiple branches of the vagus nerve trunk can be separated and identified.
  • RLN 106 and the remaining part of the vagus nerve are isolated and instrumented with individual nerve cuff electrodes 538 (on or adjacent to RLN 106) and 536 (on or adjacent to tVN 104).
  • a tripolar nerve cuff electrode 566 is implanted on cervical vagus nerve trunk 102 to record antidromic ENG activity, and an electrode 556 including a pair of insulated stainless steel wires was inserted into laryngeal muscle 107 (e.g., the posterior cricoarytenoid muscle) to measure laryngeal EMG.
  • laryngeal muscle 107 e.g., the posterior cricoarytenoid muscle
  • a first neurostimulator 520A is electrically connected to electrode 536 to deliver electrical stimulation pulses to tVN 104.
  • a second neurostimulator 520B is electrically connected to electrode 538 to deliver electrical stimulation pulses to RLN 106.
  • An example for each of first neurostimulator 520A and second neurostimulator 520B is neurostimulator 220 as discussed above.
  • first neurostimulator 520A and second neurostimulator 520B may include one device being used as first neurostimulator 520A and second neurostimulator 520B at different times, or two devices that can be used concurrently or at different times.
  • First neurostimulator 520A and second neurostimulator 520B may each be an implantable device or an external device that is electrically coupled to the corresponding electrode via an implantable or percutaneous lead.
  • a neural sensing circuit 560 is electrically coupled to electrode 566 and senses a stimulation-evoked ENG signal representative of a response of cervical vagus nerve trunk 102 to the electrical stimulation pulses delivered to tVN 104 and the electrical stimulation pulses delivered to RLN 106.
  • An ENG parameter producer 562 produces an amplitude of the ENG signal indicative of the response of cervical vagus nerve trunk 102 using the sensed ENG signal.
  • a myoelectric sensing circuit 550 is electrically coupled to electrode 556 and senses a stimulation-evoked EMG signal indicative of the response to the electrical stimulation pulses delivered to tVN 104 and the electrical stimulation pulses delivered to RLN 106.
  • An EMG parameter producer 552 produces an amplitude of the EMG signal indicative of the response of the laryngeal muscle using the sensed EMG signal.
  • FIGS. 6A and 6B are illustrations of results of testing method 400.
  • the feasibility of selectively activating individual branches of the vagus nerve was investigated using a canine model and system 500.
  • FIGS. 6A and 6B show recruitment curves obtained by recording the stimulation-evoked ENG and EMG activities, which demonstrates a clear separation of nerves innervating the larynx from those of the vagus nerve that continued distally into the thorax.
  • the activation of laryngeal EMG activity above 4 mA indicates that the threshold at which the tVN stimulation current spills over into the adjacent RLN branch, thus indicating a need to adjust stimulation intensity.
  • spatially selective VNS is applied by selecting a stimulation site on a specific nerve branch and a stimulation intensity to substantially activate the one or more target branches of the vagus nerve without substantially activating one or more non-target branches of the vagus nerve.
  • a nerve is substantially activated when the stimulation-evoked neural response is detectable (such as when the amplitude of an ENG signal is at or above a specified ENG threshold) or when a stimulation-evoked response being a physiological function controlled by the nerve is detectable (such as when the amplitude of the EMG signal is at or above a specified EMG threshold).
  • a nerve is not substantially activated when the stimulation-evoked neural response is not detectable (such as when the amplitude of an ENG signal is below a specified ENG threshold) or when a stimulation-evoked response being a physiological function controlled by the nerve is detectable (such as when the amplitude of the EMG signal is below a specified EMG threshold).
  • FIG. 7 is a flow chart illustrating an embodiment of a method 700 of spatially selective VNS.
  • method 700 is performed using system 100 including its embodiments discussed in this document, with electrode 136 being a multi-contact electrode.
  • a multi-contact electrode is placed on cervical vagus nerve trunk 102 cranial to the location where tVN 104 and RLN 106 diverge.
  • the contacts of the multi-contact electrode are distributed to allow selective stimulation of the fascicles of cervical vagus nerve trunk 102.
  • one or more contacts of the multi-contact electrode are selected for substantially activating one or more target branches of the vagus nerve without causing contraction of a laryngeal muscle that is innervated by RLN 106.
  • Electrical stimulation pulses are delivered through various contacts or combination of contacts to identify the one or more contacts to be selected.
  • Stimulation control circuit 242 controls the delivery of the electrical stimulation pulses using the plurality of stimulation parameters including one or more stimulation parameters specifying the selection of the one or more contacts of the multi-contact electrode.
  • Parameter adjuster 244 adjusts the one or more stimulation parameters during the process of selecting the one or more contacts.
  • the one or more stimulation parameters specifying the one or more contact selected at completion of this process are stored in storage circuit 246 for the subsequent VNS therapy.
  • the electrical stimulation pulses are delivered using at least two contacts of the multi-contact electrode used as a bipolar electrode. In another embodiment, the electrical stimulation pulses are delivered using at least one contact of the multi-contact electrode used as a monopolar electrode and a separate electrode.
  • this process of selecting the one or more contacts includes sensing signals representative and/or indicative of the neural responses to the delivery of the stimulation pulses.
  • a stimulation-evoked electroneurographic (ENG) signal representative of a response of the cervical vagus nerve trunk to the electrical stimulation pulses is sensed, and a stimulation-evoked electromyographic (EMG) indicative of the response of the RLN to the electrical stimulation pulses is sensed.
  • the one or more target branches of the vagus nerve are considered to be substantially activated when the amplitude of the ENG signal exceeds a specified ENG threshold.
  • the process of selecting the one or more contacts includes sweeping through various contacts and/or combination of contacts of the multi-contact electrode and observing the effect of the adjustment on the amplitude of the ENG signal and the amplitude of the EMG signal.

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Claims (8)

  1. Système (500) pour stimuler un nerf vague qui comporte de multiples ramifications, le système comprenant :
    une première électrode (536) qui est configurée de manière à ce qu'elle soit placée sur une première ramification du nerf vague afin de permettre la délivrance d'impulsions de stimulation électrique à la première ramification ;
    une seconde électrode (538) qui est configurée de manière à ce qu'elle soit placée sur une seconde ramification du nerf vague afin de permettre la délivrance d'impulsions de stimulation électrique à la seconde ramification ;
    un circuit de détection neurale (560) qui est configuré de manière à ce qu'il détecte un signal électro-neurographique (ENG) provoqué par stimulation qui est représentatif d'une réponse du nerf vague aux impulsions de stimulation électrique ;
    une électrode de détection d'ENG (566) qui est une électrode à manchon ou ballonnet de stimulation de nerf tripolaire qui est couplée au circuit de détection neurale pour détecter le signal ENG provoqué par stimulation ;
    un dispositif de production de paramètre d'ENG (562) qui est configuré de manière à ce qu'il produise une amplitude du signal ENG ;
    un circuit de détection myoélectrique (550) qui est configuré de manière à ce qu'il détecte un signal électromyographique (EMG) provoqué par stimulation qui est représentatif d'une réponse d'un muscle aux impulsions de stimulation électrique, le muscle étant innervé par une seconde ramification du nerf vague ;
    une électrode de détection d'EMG (556) qui inclut une paire de fils qui sont couplés au circuit de détection myoélectrique pour détecter le signal EMG provoqué par stimulation ;
    un dispositif de production de paramètre d'EMG (552) qui est configuré de manière à ce qu'il produise une amplitude du signal EMG ; et
    un premier neuro-stimulateur (220 ; 520A) et un second neuro-stimulateur (220 ; 520B), chacun d'eux incluant :
    un circuit de stimulation (240) qui est configuré de manière à ce qu'il délivre les impulsions de stimulation électrique à la ramification du nerf vague par l'intermédiaire de l'électrode ; et
    un circuit de commande de stimulation (242) qui est configuré de manière à ce qu'il commande la délivrance des impulsions de stimulation électrique en utilisant une pluralité de paramètres de stimulation, le circuit de commande de stimulation incluant un dispositif de réglage de paramètre (244) qui est configuré de manière à ce qu'il permette le réglage d'un ou de plusieurs paramètre(s) de stimulation de la pluralité de paramètres de stimulation en utilisant le signal ENG et le signal EMG ; dans lequel :
    le circuit de stimulation (240) du premier neuro-stimulateur (220, 520A) est configuré de manière à ce qu'il délivre les impulsions de stimulation électrique à la première ramification du nerf vague et le circuit de stimulation (240) du second neuro-stimulateur (220, 520B) est configuré de manière à ce qu'il délivre les impulsions de stimulation électrique à la seconde ramification du nerf vague.
  2. Système selon la revendication 1, dans lequel la première électrode (536) comprend une électrode à manchon ou ballonnet.
  3. Système selon l'une quelconque des revendications 1 et 2, dans lequel le circuit de commande de stimulation comprend un circuit de stockage (246) qui est configuré de manière à ce qu'il stocke les un ou plusieurs paramètres de stimulation qui sont réglés pour une amplitude du signal ENG qui excède un seuil d'ENG spécifié et pour une amplitude du signal EMG qui est au-dessous d'un seuil d'EMG spécifié.
  4. Système selon la revendication 1, dans lequel le dispositif de réglage de paramètre (244) est configuré de manière à ce qu'il règle une amplitude impulsionnelle qui est une amplitude de chaque impulsion des impulsions de stimulation électrique.
  5. Système selon la revendication 1, dans lequel le dispositif de réglage de paramètre (244) est configuré de manière à ce qu'il règle une largeur impulsionnelle qui est une durée de chaque impulsion des impulsions de stimulation électrique.
  6. Système selon la revendication 1, dans lequel le dispositif de réglage de paramètre (244) est configuré de manière à ce qu'il règle une fréquence impulsionnelle qui est une fréquence à laquelle les impulsions de stimulation électrique sont délivrées.
  7. Système selon la revendication 1, dans lequel le dispositif de réglage de paramètre (244) est configuré de manière à ce qu'il règle un rapport cyclique selon lequel les impulsions de stimulation électrique sont délivrées.
  8. Système selon la revendication 1, dans lequel le premier neuro-stimulateur (520A) et le second neuro-stimulateur (520B) incluent un seul dispositif qui est configuré de manière à ce qu'il soit utilisé en tant que premier neuro-stimulateur (520A) et que second neuro-stimulateur (520B) à des instants différents, ou deux dispositifs qui sont configurés de manière à ce qu'ils soient utilisés concurremment ou à des instants différents.
EP11725562.0A 2010-06-03 2011-05-24 Système de stimulation spatialement sélective du nerf vague Not-in-force EP2575961B1 (fr)

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US8942824B2 (en) 2015-01-27
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JP2013530747A (ja) 2013-08-01
US20130310893A1 (en) 2013-11-21
US8509919B2 (en) 2013-08-13
EP2575961A1 (fr) 2013-04-10

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